Announcement
TypeThis
is a reissue of PA-01-073, which was
previously released March 20, 2001.

Update: The following update relating to this announcement has been issued:

November 27, 2009 - See Notice NOT-MH-10-006 NIMH Announces Changes in NIMH Participation, As of January 8, 2010, NIMH will terminate or withdraw its participation from this FOA.

NOTICE: Applications submitted in response to this Funding
Opportunity Announcement (FOA) for Federal assistance must be submitted
electronically through Grants.gov (http://www.grants.gov)
using the SF424 Research and Related (R&R) forms and the SF424 (R&R)
Application Guide.

APPLICATIONS MAY NOT BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in conjunction with the
application guidelines included with this announcement in Grants.gov/Apply
for Grants (hereafter called Grants.gov/Apply).

A registration process is necessary before submission
and applicants are highly encouraged to start the process at least four weeks
prior to the grant submission date. See Section IV.

Purpose.This funding opportunity
announcement (FOA) issued by the National Institute of Mental Health,
National Institute on Drug Abuse, and National Institute of Nursing
Research invites grant applications from applicant organizations to advance scientific research and intervention
regarding HIV treatment adherence.

Mechanism of
Support. This FOA will utilize the NIH Research Project Grant (R01) award
mechanism and runs in parallel with FOAs of similar scientific scope, PA-07-339which
solicits applications under the Small Research Grant (R03) mechanism; PA-07-340, which
solicits applications under the
Exploratory/Developmental (R21) mechanism; and PAR-07-341, which
solicits applications under the Exploratory Grants for Mental Health
Interventions and Services (R34) mechanism.Please note that the participating
organizations vary across this set of FOAs.

Funds
Available and Anticipated Number of Awards. Awards issued under this FOA are
contingent upon the availability of funds and the submission of a sufficient number of meritorious applications.

Applications
can be renewed by competing for additional project periods.

Eligible Project
Directors/Principal Investigators (PDs/PIs).Individuals with the
skills, knowledge, and resources necessary to carry out the proposed
research are invited to work with their institution/organization to
develop an application for support. Individuals from underrepresented
racial and ethnic groups as well as individuals with disabilities are
always encouraged to apply for NIH support.

Number of
Applications. Applicants may submit more than one application,
provided each application is scientifically distinct.

Renewals and
Resubmissions. Applications can be renewed by competing for
additional project periods. Applicants may submit a “resubmission”
application, but such application must include an “Introduction”
addressing the previous peer review critique (Summary Statement).

Number of PDs/PIs. More than one PD/PI, or
multiple PDs/PIs, may be designated on the application.

This funding
opportunity announcement (FOA) calls for research to advance the scientific
understanding of HIV treatment adherence and to enhance and expand available
intervention strategies to promote, improve, and
sustain adherence. The overarching emphasis is on the development of
innovative behavioral and structural adherence interventions that could be
rapidly translated into clinical practice, community venues, and public health policy within domestic and international
settings. Any descriptive studies should therefore be undertaken with the aim
of informing the mechanisms of adherence interventions. Interventions may
target patient adherence to antiretroviral medications
or other aspects of HIV treatment that can be shown to affect patient outcomes
and public health (e.g., linkage to primary care, medical appointment
attendance, and service utilization). Investigators are encouraged to consider
incorporation of clinical outcomes (e.g., viral load,
CD4 T-cell count, drug resistance) into intervention trials when feasible and
scientifically appropriate. Studies are also needed that will advance
knowledge of effective approaches for promoting the dissemination, adoption, and sound implementation of tested adherence
interventions. A well-articulated and empirically based conceptual framework
is essential for all applications solicited under this announcement.
Approaches based on basic behavioral and social scientific principles such as cognition, emotion, decision-making,
motivation, social interaction, structural factors, and cultural context are
invited. Proposals for interdisciplinary and community-collaborative research
addressing HIV treatment adherence are particularly
encouraged.

BACKGROUND

The efficacy of
combination antiretroviral therapies (ART) for the treatment of HIV disease has
been well documented. ART can inhibit viral replication and reduce viral load
to a point where viral particles are undetectable in
the blood plasma of infected individuals. Sustained suppression of HIV
replication and associated increases in CD4 T-cell count are strongly
associated with improved patient outcomes. The efficacy of ART has produced
dramatic declines in HIV/AIDS-related mortality in
nations where ART is widely available.

Optimal clinical
benefits associated with ART, however, demand rigorous adherence to medication
dosing schedules and other aspects of treatment. Among many factors that can
influence treatment success or failure, research has
identified high adherence to ART regimens as the most important predictor of
viral suppression, improved CD4+ T-cell count, delayed progression to AIDS, and
patient survival. Although more potent medication regimens can allow for effective viral suppression at moderate levels of
adherence, improving adherence to any degree can only increase the likelihood
of suppressing the virus and postponing disease progression. Striving for the
highest possible level of adherence therefore remains
essential for optimizing HIV treatment outcomes.

The importance
of treatment adherence for patient health is complemented by the importance of
adherence for the public health. Partial or poor ART adherence can lead to the
resumption of rapid viral replication and the
development of mutant viral strains that are resistant to available
antiretroviral drugs. The development and transmission of these drug-resistant
strains of HIV can limit the treatment options available to newly-infected
individuals. Drug-resistant HIV can additionally
hamper the wide scale provision of treatment within resource-poor nations by
compromising the use of affordable first-line therapies.

Despite the
critical need for strong HIV treatment adherence, research indicates that many patients have difficulty realizing this goal. A
meta-analysis of 59 studies conducted in North America and Africa reported that only
55% of North American patients demonstrated high levels of ART adherence (Mills
et al., 2006). The percentage of African patients
who achieved high adherence was more favorable (77%), but this proportion could
decline over time as patients initiating therapy encounter the challenges of
maintaining long-term adherence, and as treatment availability in these nations expands beyond those with early access to ART.

The
understanding and enhancement of HIV treatment adherence within domestic and
international settings therefore represents a vital goal for individuals
receiving treatment, for those providing treatment, for
health officials responsible for making treatment available, and for the public
health at-large. Scientists and practitioners have made significant gains in
assessing, understanding, and promoting adherence in recent years, but critical
gaps remain in our knowledge and abilities for
advancing HIV treatment adherence. Research is urgently needed to address
these gaps and other longstanding challenges facing the field in order to
strengthen and sustain approaches for maintaining high treatment adherence among HIV-seropositive patients.

RESEARCH SCOPE

This funding
opportunity announcement (FOA) calls for a broad range of research that will
help patients achieve and maintain close adherence to ART and other important
aspects of medical care. A set of key challenges and
gaps within the existing scientific literature are discussed below. This list
of priority areas is neither comprehensive nor restrictive; it is offered to
stimulate critical thinking and innovative approaches on HIV treatment
adherence.

Formative Research and Theory Development

Empirical
studies and theory development have elaborated important determinants of
adherence to ART, particularly within Western clinic populations. The specific
factors associated with adherence vary across patients,
contexts, and time, but some of the most commonly reported factors include
regimen complexity, side effects, patient motivation, self-efficacy,
depression, substance abuse, and forms of social support. These findings, when
combined with prior theory and research on other
chronic disease conditions, have informed good working models for understanding
and enhancing adherence to ART.

The conduct of
formative research and the articulation of theoretical models are critical for
designing effective adherence interventions. The
preponderance of this scholarship to date, however, has focused on
individual-level predictors of patient adherence (e.g., psychosocial factors,
personality traits, behavioral correlates, and treatment characteristics).

Comparatively fewer studies have systematically investigated various
provider, system, and contextual-level variables, despite evidence that these
factors can affect access to treatment and adherence to ART. For example,
emerging research within multiple resource-limited
countries has underscored the role of structural barriers to adherence,
including treatment costs, food insecurity, and interruptions in drug stocks
and prescription refills. To better inform future adherence interventions,
more research will be needed to understand these and
other structural determinants of adherence in both domestic and international
settings. Research relevant to this point may include, but is not limited to,
the following:

Research addressing structural barriers
and facilitators of treatment adherence, including
economic considerations, food security, housing, neighborhood characteristics,
service provision (including drug abuse treatment provision), and institutional
policies; these studies should link directly to the development and testing of interventions to modify these mechanisms
or their impact.

Research using cross-national designs to
compare large-scale structural, environmental, governmental, and cultural
factors that may contribute to treatment adherence.

Formative research
on social, situational, societal factors that may hold proximal or distal
relationships with treatment adherence, including aspects of social support
networks, serostatus disclosure, HIV/AIDS stigma and discrimination, the
acceptability and availability of drug abuse
treatment programs and services, and gender and racial inequality.

Research to understand how and why
integrated service delivery systems contribute to effective patient adherence.

Research on forms of treatment
patient-provider-caregiver alliances, how these
partnerships may affect adherence to medication regimens, and identification of
the active ingredients of effective partnerships.

Research on provider behavior and skills
in working with marginalized or stigmatized drug-abusing individuals who have complex therapeutic regimens.

Research on the manner in which
co-morbid conditions may affect HIV treatment adherence, such as depression,
substance abuse, side-effects (e.g., fatigue, metabolic issues), TB, and HCV,
as well as conditions that may be associated with
long-term treatment or even aging (e.g., diabetes, cardiovascular disease,
neuropathy).

Research to expand understanding of the
complex interplay between individual-level and structural-level mechanisms
associated with adherence and non-adherence within
particular domestic and international populations.

Novel Adherence
Interventions

Research to date
has generated a growing set of interventions with demonstrated efficacy in
improving ART adherence. The first meta-analyses of this adherence intervention research have now been conducted, and their
results are generally favorable. For example, a meta-analysis of 19 randomized
controlled trials of ART adherence interventions found that participants who
received an intervention were 1.5 times as likely to
report 95% adherence and 1.25 times as likely to achieve an undetectable viral
load than those in comparison conditions (Simoni, Pearson, Pantalone, Marks,
& Crepaz, 2006).

Further research
is necessary to expand the available interventions for HIV treatment adherence and enhance their efficacy. Documented
intervention effects to date have generally been modest, and research trials
incorporating extended follow-up periods often show that observed intervention
effects decline over time. An important goal for new
adherence research is therefore to identify and promote innovative methods for
the long-term maintenance of patient adherence. In addition, the range of
efficacious and non-efficacious adherence interventions remains so wide that it
is not yet entirely clear what mechanisms are
responsible for the observed successes or failures. Future intervention
studies should therefore be powered to determine mediators of intervention
efficacy, and could be designed to help evaluate reasons why certain interventions work and others do not work.

Developing
effective interventions with sustained impact will require innovative
approaches for promoting HIV treatment adherence. These studies include, but
are not limited to, the following:

Research on innovative
approaches for sustaining long-term adherence through structural interventions,
relapse prevention models, new technologies, or the integration of adherence
support into ongoing care.

Research on potential challenges to HIV
treatment adherence among people coping with
co-morbid conditions, such as depression, substance abuse, HCV, TB, or common
side-effects (e.g., fatigue, metabolic issues), as well as conditions that may
be associated with long-term treatment or even aging (e.g., diabetes, cardiovascular disease, neuropathy). Intervention studies for
meeting these challenges are encouraged.

Research designed to match adherence
intervention strategies to the specific needs of individual patients (e.g.,
drug dependent individuals with cognitive impairments
or with serious and persistent mental illness).

Research on the relationship(s) among
disease stage, adherence, and treatment response to identify points in the
course of HIV disease where different types of adherence interventions can have
the greatest impact.

Research on novel,
electronically-mediated methods of delivering adherence interventions and
assessments to geographically or socially isolated
populations.

Research on pharmacogenetics and
pharmacokinetics to facilitate the tailoring ART regimens to individual
patients in a manner that may help to ameliorate drug toxicities and side
effects, as well as the clinical implications of
imperfect adherence.

Research to conduct secondary analyses
to understand mediators and moderators of observed intervention effects.

Translational intervention development
based upon social, cognitive, or affective neuroscience research

The National
Institute on Drug Abuse’ Clinical Trials Network (CTN) offers an ideal clinical
research platform for multicenter, multidisciplinary
national studies on HIV treatment adherence in the drug abuse population. The
following types of studies are encouraged:

Easy-to-administer, cognitive-behavioral
interventions designed to increase adherence to HIV medication among patients
with HIV in drug treatment setting.

Existing HIV
treatment adherence research has primarily targeted patient adherence to daily
ART dosage requirements as assessed through a variety of methods. Aspects of
treatment adherence other than daily medication
taking behavior, however, remain comparatively unstudied and may offer
potentially important contributions to patient care and clinical outcomes.

For example,
additional aspects of ART regimens may merit consideration. One concerns ART initiation. Indications of continued racial
and ethnic disparities in ART initiation among eligible patients will require
additional research to understand how both treatment providers and patients
make decisions about when to start therapy. Further
empirical research on effective approaches for preparing patients to initiate
ART treatment may also be useful. A second consideration is inopportune ART
treatment discontinuations or interruptions. Notable proportions of patients
who initiate ART discontinue their treatment within
one to two years due to side effects, psychosocial issues, or virologic
failure. These discontinuations have been associated with deleterious clinical
outcomes, particularly in patients with limited immune reconstitution. Interventions expressly designed to prevent the
outcome of inopportune treatment discontinuations in vulnerable patients could
therefore be helpful. A final example relates to ART drug stocks,
distribution, and refills. Under a structural approach, interventions could potentially assist medication adherence by
stabilizing available drug stocks in resource-limited settings and facilitating
the timely provision of prescription refills.

Research on HIV
treatment adherence should additionally broaden beyond
aspects of medication-taking. A broad, multidimensional understanding of HIV
treatment adherence argues for addressing important aspects of patient care
other than ART. Many patients never initiate care after testing HIV
seropositive, and those who enroll in HIV treatment
often do not attend enough medical appointments to benefit. In addition, many
HIV+ patients have unmet needs for services such as housing, public assistance,
and psychiatric and substance abuse treatment, and these unmet needs have been associated with decreased likelihood of ART use and
poor ART adherence. To complement the ongoing research on adherence to ART
medications, innovative interventions to increase consistent utilization of HIV
care and social services are needed.

Research designed to broaden the outcomes targeted by HIV
adherence interventions may therefore encompass, but is not limited to, the
following:

Research to refine measurements of
different forms of ART adherence (e.g., studies that account for the myriad of biological and health behavioral outcomes that can
influence CD4 count and viral load, in the context of treatment and adherence
interventions, in order to identify appropriate intervention outcomes).

Research to assess ART regimen-specific
adherence requirements for virological suppression
and avoiding development of drug resistance.

Research to encourage appropriate and
effective initiation of ART regimens when indicated, and to further understand
and minimize premature or inopportune ART discontinuations or interruptions.

Research to improve the skills and
effectiveness of medical providers for assessing patient ART adherence and
conducting interventions to promote adherence. Whenever possible, both
provider and patient outcomes should be included.

Research
designed to aid patient care and clinical outcomes by addressing linkage to
primary care, consistent attendance at medical appointments, and follow-through
on referrals for ancillary care, such as mental health services, substance
abuse treatment, and other social services.

Research to promote timely prescription
refills and continuity of drug stocks for the purpose of sustaining
uninterrupted patient adherence.

Research in
International Settings and with Underserved Populations

After the first
decade of HAART, the published randomized controlled
trials of adherence interventions have been conducted in North America and Europe. Outside of these
regions, ART rollout is occurring rapidly in many countries. There is an
urgent need for further research to understand the
mechanisms that shape treatment adherence in these settings. Studies that will
develop and test sustainable, culturally-appropriate interventions within
resource-limited settings are also critically important.

A related
population of global concern is children and
adolescents. Sizable populations of HIV-infected children and adolescents
exist in many nations. Some of the first descriptions of adherence rates for
children in resource-constrained settings suggest lower rates than has been observed for adults, suggesting that special efforts may
be required to advance and maintain support for adherence in these groups.
Within the U.S., the
number of HIV diagnoses among youth has also been increasing over the past few
years, particularly among teenage girls and
minorities. Both domestically and internationally, developmental
considerations and family dynamics are important factors that require closer
examination as to their impact on ART adherence among children and adolescents.

Other specific groups could additionally benefit from effective
adherence interventions. Innovative, effective interventions are needed to
improve ART adherence and prevent drug treatment relapse among the severely
mentally ill and both injecting and non-injecting
drug users. Although persons with severe mental illness are at enhanced risk
for HIV, relatively little is known about their ART adherence and such issues
as interactions of ART medications with psychoactive medications. Among drug
abusers, there are few data on potential risks of
toxicity and drug interactions between illicit drugs and HIV therapies, as well
as pharmacotherapies for substance abuse, mental health conditions, and other
diseases. These interactions may influence adherence, reduce the effectiveness of HIV treatment, and cause morbidity.

Studies
addressing HIV treatment adherence within international settings and with
underserved populations may then include, but are not restricted to, the
following:

Studies to develop, adapt, and assess
theory-based interventions for improving adherence
among underserved, high risk, or special need populations (e.g., persons with
severe mental illness, drug and alcohol users, individuals transitioning from
inpatient drug treatment or correctional facilities, children and adolescents).

Research to develop
and test culturally appropriate HIV treatment adherence interventions among
specific racial and ethnic minority groups, and interventions that will address
racial and ethnic disparities in access or linkage to care.

Studies on interventions designed to improve ART adherence among children and adolescents,
which could be delivered through various modalities including family, peers, or
instructional video games.

Descriptive studies undertaken with the
express aim of informing the development or tailoring of adherence interventions for any other underserved or at-risk
patient populations and care settings.

Promoting the
Translation of Efficacious Interventions into Practice

Translational
research in the adherence domain could benefit from additional work. Relatively little is known about contextual issues that affect
intervention adoption, adaptation, and effectiveness of adherence interventions
that were tested in randomized clinical trials (RCTs). Organizational
leadership, clinic personnel turnover, and organizational
size are factors that may influence implementation of new interventions. An
additional consideration for research is that, whether intentional or
unintentional, interventions will be modified in real-world settings. The
effectiveness of HIV treatment adherence
interventions implemented outside of rigorous RCTs may rely on how well
fidelity to the intervention protocols can be maintained in the face of
competing clinic demands. How best to measure success in translational
research also needs examination; success could be
defined as whether or not an intervention is adopted and sustained for a
specified time period, and/or success could be measured through direct
assessment of patient outcomes.

Translational
research in the adherence domain may include, but is
not limited to, the following examples:

Studies of designed to promote and
sustain the adoption of efficacious adherence interventions in clinical
settings, including drug abuse treatment settings.

Studies to assess the effectiveness of
adherence interventions in real-world settings in relationship to intervention
fidelity vs. adaptation

Studies to understand the
cost-effectiveness of adherence interventions.

Understanding
the Intersections of HIV Treatment Adherence and Prevention

Recent years
have brought increasing recognition of “prevention for positives” as a key
component of comprehensive HIV prevention in the U.S. and elsewhere. This necessarily
involves behavioral interventions and risk reduction counseling, but treatment
adherence may also have a role to play. Adherence to ART treatment can yield
reductions in viral load that may help to reduce infectivity, which suggests that efforts to sustain medication adherence could
potentially assist the goal of HIV prevention. At the same time, some studies
suggest that patients with poor ART adherence are also likely to engage in
unprotected sex. This confluence suggests that
simultaneous attention to both issues may help to prevent transmission of drug
resistant viral strains to uninfected individuals. Future initiatives are
indicated to integrate risk reduction counseling and adherence interventions
into the provision of primary care and services for
HIV+ individuals. In addition, emerging biomedical prevention strategies
targeted to HIV seronegative individuals, such as post-exposure prophylaxis
(PEP) and pre-exposure prophylaxis (PrEP), present new domains where understanding and promoting medication adherence may be critical for
preventing new HIV infections.

Studies are
needed that will further investigate important intersections between HIV
treatment adherence and HIV prevention, including but not limited to:

Research addressing
beneficial and deleterious changes in behavioral risk-taking that may occur as
a result of adherence to ART and of the factors that influence long-term
therapeutic effectiveness, development of viral resistance, disease
progression, and medical outcomes in high-risk
individuals.

Research to model the potential impact
of ART treatment and adherence interventions on HIV transmission and new
infections on a population level.

Research to integrate treatment
adherence and behavioral risk reduction interventions.

Research to integrate HIV treatment
adherence and drug abuse treatment and prevention interventions.

Research designed to understand and
promote patient adherence to post-exposure and pre-exposure prophylaxis when
indicated.

The areas
identified above represent only a small set of
priority areas to help advance HIV treatment research. Studies are needed to
address these issues as well as a wide variety of other domains to further our
scientific understanding of efforts to foster, improve, and sustain HIV treatment adherence.

This Funding Opportunity Announcement (FOA) will use
the NIH Research Project Grant (R01) award mechanism. The applicant will be solely
responsible for planning, directing, and executing the proposed project.

Specifically, if you are a U.S. organization and are
submitting an application with direct costs in each year of $250,000 or less (excluding consortium Facilities
and Administrative [F&A] costs), use the PHS398 Modular Budget component
provided in the SF424 (R&R) Application Package and SF424 (R&R)
Application Guide (see specifically Section 5.4, “Modular Budget Component,” of
the Application Guide).

U.S. applicants requesting more than
$250,000 in annual direct costs and all foreign applicants must complete and
submit budget requests using the Research & Related Budget component found
in the application package for this FOA. See NOT-OD-06-096,
August 23, 2006.

2. Funds Available

Because the nature and scope
of the proposed research will vary from application to application, it is
anticipated that the size and duration of each award will also vary. Although
the financial plans of the Institutes and Centers (ICs) provide support for
this program, awards pursuant to this funding opportunity are contingent upon
the availability of funds and the submission of a sufficient number of
meritorious applications.

NIH grants policies as described in the NOT-OD-05-004,
November 2, 2004.

Section
III. Eligibility Information

1. Eligible Applicants

1.A. Eligible
Institutions

You may submit an
application(s) if your institution/organization has any of the following
characteristics:

Indian/Native American Tribal Government
(Other than Federally Recognized)

Indian/Native American Tribally Designated
Organization

Non-domestic (non-U.S.) Entity (Foreign
Organization)

Hispanic-serving Institution

Historically
Black Colleges and Universities (HBCUs)

Tribally Controlled Colleges and
Universities (TCCUs)

Alaska Native and Native
Hawaiian Serving Institutions

Regional Organization

1.B. Eligible Individuals

Any individual(s) with the
skills, knowledge, and resources necessary to carry out the proposed research
as the PD/PI is invited to work with his/her organization to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.

More than one PD/PI, or multiple PDs/PIs, may be
designated on the application for projects that require a “team science”
approach that clearly does not fit the single-PD/PI model. Additional
information on the implementation plans and policies and procedures to formally
allow more than one PD/PI on individual research projects is available athttps://grants.nih.gov/grants/multi_pi. All PDs/PIs must be registered in the NIH eRA Commons prior
to the submission of the application (seehttp://era.nih.gov/ElectronicReceipt/preparing.htmfor instructions).

The decision of whether to
apply for a single PD/PI or multiple PD/PI grant is the responsibility of the
investigators and applicant organizations and should be determined by the
scientific goals of the project. Applications for multiple PD/PI grants will
require additional information, as outlined in the instructions below. The NIH
review criteria for approach, investigators, and environment have been modified
to accommodate applications involving either a single PD/PI or multiple
PDs/PIs. When considering multiple PDs/PIs, please be aware that the structure
and governance of the PD/PI leadership team as well as the knowledge, skills
and experience of the individual PD/PIs will be factored into the assessment of
the overall scientific merit of the application. Multiple PDs/PIs on a project
share the authority and responsibility for leading and directing the project,
intellectually and logistically. Each PD/PI is responsible and accountable
to the grantee organization, or, as appropriate, to a collaborating
organization, for the proper conduct of the project or program, including the
submission of required reports. For further information on multiple PDs/PIs,
please seehttps://grants.nih.gov/grants/multi_pi.

The individual(s) designated as
PDs/PIs on the application must also be registered in the NIH eRA Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and be assigned the
PI role in the eRA Commons prior to the submission of the application.

Each PD/PI must hold a PD/PI
account in the Commons. Applicants should not share a Commons account for both
an Authorized Organization Representative/Signing Official (AOR/SO) role and a
PD/PI role; however, if they have both a PD/PI role and an Internet Assisted
Review (IAR) role, both roles should exist under one Commons account.

When multiple PDs/PIs are
proposed, all PDs/PIs at the applicant organization must be affiliated with
that organization. PDs/PIs located at another institution need not be
affiliated with the applicant organization, but must be affiliated with their
own organization to be able to access the Commons.

This registration/affiliation must
be done by the AOR/SO or their designee who is already registered in the Commons.

Both the PD/PI(s) and AOR/SO need separate accounts in
the NIH eRA Commons since both are authorized to view the application image.

Note that if a PD/PI is also an NIH peer-reviewer with
an Individual DUNS and CCR registration, that particular DUNS number and CCR
registration are for the individual reviewer only. These are different than any
DUNS number and CCR registration used by an applicant organization. Individual
DUNS and CCR registration should be used only for the purposes of personal
reimbursement and should not be used on any grant applications submitted to the
Federal Government.

Several of the steps of the registration process could
take four weeks or more. Therefore, applicants should immediately check with
their business official to determine whether their organization/institution is
already registered in both Grants.gov and
the Commons. The NIH will
accept electronic applications only from organizations that have completed all
necessary registrations.

1. Request Application Information

Applicants must
download the SF424 (R&R) application forms and the SF424 (R&R)
Application Guide for this FOA through Grants.gov/Apply.

Note: Only the forms package
directly attached to a specific FOA can be used. You will not be able to use
any other SF424 (R&R) forms (e.g., sample forms, forms from another FOA),
although some of the "Attachment" files may be useable for more than
one FOA.

Prepare all applications using the SF424 (R&R)
application forms and in accordance with the SF424
(R&R) Application Guide for this FOA through Grants.gov/Apply.

The SF424 (R&R) Application Guide is critical to
submitting a complete and accurate application to NIH. There are fields within
the SF424 (R&R) application components that, although not marked as
mandatory, are required by NIH (e.g., the “Credential” log-in field of the
“Research & Related Senior/Key Person Profile” component must contain the
PD/PI’s assigned eRA Commons User ID). Agency-specific instructions for
such fields are clearly identified in the Application Guide. For additional information,
see “Frequently Asked Questions – Application Guide, Electronic
Submission of Grant Applications.”

The SF424 (R&R) application has several
components. Some components are required, others are optional. The forms
package associated with this FOA in Grants.gov/APPLYincludes all applicable components, required and optional. A completed
application in response to this FOA includes the data in the following
components:

Format: Every effort
should be made to comply with the format specifications, which are based
upon a standard U.S. paper size of 8.5” x 11” within each PDF.

Funds for up to 8%
administrative costs (excluding equipment) may be requested. SeeNOT-OD-01-028, March 29, 2001.

Organizations must
comply with Federal/NIH policies on human subjects, animals, and
biohazards.

Organizations must
comply with Federal/NIH biosafety and biosecurity regulations. See Section VI.2., “Administrative and National Policy Requirements.”

Proposed research should provide
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions in other
countries that are not readily available in the United States or that augment
existing U.S. resources.

SPECIAL INSTRUCTIONS

Applications with Multiple PDs/PIs

When multiple PDs/PIs are proposed, NIH requires one
PD/PI to be designated as the "Contact” PI, who will be responsible for
all communication between the PDs/PIs and the NIH, for assembling the
application materials outlined below, and for coordinating progress reports for
the project. The contact PD/PI must meet all eligibility requirements for PD/PI
status in the same way as other PDs/PIs, but has no other special roles or
responsibilities within the project team beyond those mentioned above.

Information for the Contact PD/PI should be entered in
item 15 of the SF424(R&R) Cover component. All other PDs/PIs should be
listed in the Research & Related Senior/Key Person component and assigned
the project role of “PD/PI.” Please remember that all PDs/PIs must be
registered in the eRA Commons prior to application submission. The Commons ID of each PD/PI must be included in the “Credential” field of the Research &
Related Senior/Key Person component. Failure to include this data field
will cause the application to be rejected.

All projects
proposing Multiple PDs/PIs will be required to include a new section describing
the leadership of the project.

Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, a new
section of the research plan, entitled “Multiple PD/PI Leadership Plan”
(section 14 of the Research Plan Component in the SF424 (R&R) or Section I
of the Research Plan in the PHS 398), must be included. A rationale for
choosing a multiple PD/PI approach should be described. The governance and
organizational structure of the leadership team and the research project should
be described, including communication plans, process for making decisions on
scientific direction, and procedures for resolving conflicts. The roles
and administrative, technical, and scientific responsibilities for the project
or program should be delineated for the PDs/PIs and other collaborators.

If budget allocation is planned, the distribution of resources to
specific components of the project or the individual PDs/PIs should be
delineated in the Leadership Plan. In the event of an award, the requested allocations
may be reflected in a footnote on the Notice of Award.

Applications Involving a Single Institution

When all PDs/PIs are within a single institution,
follow the instructions contained in the SF424 (R&R) Application Guide.

Applications Involving Multiple Institutions

When multiple institutions are involved, one
institution must be designated as the prime institution and funding for the
other institution(s) must be requested via a subcontract to be administered by
the prime institution. When submitting a detailed budget, the prime institution
should submit its budget using the Research & Related Budget
component. All other institutions should have their individual budgets
attached separately to the Research & Related Subaward Budget Attachment(s)
Form. See Section 4.8 of the SF424 (R&R) Application Guide for further
instruction regarding the use of the subaward budget form.

When submitting a modular budget, the prime
institution completes the PHS398 Modular Budget component only. Information
concerning the consortium/subcontract budget is provided in the budget
justification. Separate budgets for each consortium/subcontract grantee are not
required when using the Modular budget format. See Section 5.4 of the
Application Guide for further instruction regarding the use of the PHS398
Modular Budget component.

Applications may be submitted on or after the opening date and must be
successfully received by Grants.gov no later than 5:00 p.m. local time (of the applicant
institution/organization) on the application submission/receipt date(s). (See Section IV.3.A. for all dates.) If an application is not submitted by the receipt
date(s) and time, the application may be delayed in the review process or not
reviewed.

Once an application package has been successfully submitted through
Grants.gov, any errors have been addressed, and the assembled application has
been created in the eRA Commons, the PD/PI and the Authorized Organization
Representative/Signing Official (AOR/SO) have two business days to view the
application image.

If
everything is acceptable, no further action is necessary. The application will
automatically move forward for processing by the Division of Receipt and
Referral, Center for Scientific Review, NIH, after two business days.

Prior
to the submission deadline, the AOR/SO can “Reject” the assembled application
and submit a changed/corrected application within the two-day viewing window.
This option should be used if the AOR/SO determines that warnings should be
addressed or if information was lost or compromised during transmission.
Reminder: warnings do not stop further application processing. If an
application submission results in warnings (but no errors), it will
automatically move forward after two business days if no action is taken.
Please remember that some warnings may not be applicable or may need to be
addressed after application submission.

If
the two-day window falls after the submission deadline, the AOR/SO will have
the option to “Reject” the application if, due to an eRA Commons or Grants.gov
system issue, the application does not correctly reflect the submitted
application package (e.g., some part of the application was lost or didn’t
transfer correctly during the submission process). The AOR/SO should first
contact the eRA Commons Helpdesk to confirm the system error, document the issue, and determine the best course
of action. NIH will not penalize the applicant for an eRA Commons or Grants.gov
system issue.

If
the AOR/SO chooses to “Reject” the image after the submission deadline for a
reason other than an eRA Commons or Grants.gov system failure, a
changed/corrected application still can be submitted, but it will be subject to
the NIH
late policy guidelines and may not be accepted. The reason for this delay
should be explained in the cover letter attachment.

Both
the AOR/SO and PD/PI will receive e-mail notifications when the application is
rejected or the application automatically moves forward in the process after
two days.

Upon receipt, applications
will be evaluated for completeness by the Center for Scientific Review, NIH.
Incomplete applications will not be reviewed.

There will
be an acknowledgement of receipt of applications from Grants.gov and the Commons. The submitting AOR receives
the Grants.gov acknowledgments. The AOR and the PI receive Commons
acknowledgments. Information related to the assignment of an application to a
Scientific Review Group is also in the Commons.

Note: Since email can be
unreliable, it is the responsibility of the applicant to check periodically on
their application status in the Commons.

The NIH will not accept any
application in response to this FOA that is essentially the same as one
currently pending initial merit review unless the applicant withdraws the
pending application. The NIH will not accept any application that is
essentially the same as one already reviewed. This does not preclude the
submission of an application already reviewed with substantial changes, but
such application must include an “Introduction” addressing the previous
critique. Note such an application is considered a "resubmission" for
the SF424 (R&R).

All NIH awards are subject to
the terms and conditions, cost principles, and other considerations described
in the NIH
Grants Policy Statement.

Pre-award costs are allowable. A grantee may, at its own risk and without
NIH prior approval, incur obligations and expenditures to cover costs up to 90
days before the beginning date of the initial budget period of a new or
competing renewal (formerly “competing continuation”) award if such costs: are
necessary to conduct the project, and would be allowable under the grant, if
awarded, without NIH prior approval. If specific expenditures would otherwise
require prior approval, the grantee must obtain NIH approval before incurring
the cost. NIH prior approval is required for any costs to be incurred more than
90 days before the beginning date of the initial budget period of a new or
competing renewal award.

The incurrence of pre-award costs in
anticipation of a competing or non-competing award imposes no obligation on NIH
either to make the award or to increase the amount of the approved budget if an
award is made for less than the amount anticipated and is inadequate to cover
the pre-award costs incurred. NIH expects the grantee to be fully aware that
pre-award costs result in borrowing against future support and that such
borrowing must not impair the grantee's ability to accomplish the project
objectives in the approved time frame or in any way adversely affect the
conduct of the project. See the NIH Grants
Policy Statement.

The applicant organization
must include its DUNS number in its Organization Profile in the eRA Commons.
This DUNS number must match the DUNS number provided at CCR registration with
Grants.gov. For additional
information, see “Frequently Asked Questions – Application Guide, Electronic
Submission of Grant Applications.”

PHS398
Research Plan Component Sections

Items 2-5 of the PHS398
Research Plan component are limited to 25 pages. While each section of the
Research Plan component needs to be uploaded separately as a PDF attachment,
applicants are encouraged to construct the Research Plan component as a single
document, separating sections into distinct PDF attachments just before
uploading the files. This approach will enable applicants to better monitor
formatting requirements such as page limits. All attachments must be provided
to NIH in PDF format, filenames must be included with no spaces or special
characters, and a .pdf extension must be used.

All application instructions
outlined in the SF424 (R&R) Application Guide are to be followed,
incorporating "Just-in-Time" information concepts, and with the
following additional requirements:

Special Instructions
for Modular Grant applications

R01 applications from U.S. institutions/organizations requesting up to $250,000 per year in direct costs
(excluding consortium F&A costs) must be submitted in a modular budget
format. Additional information on modular budgets is available at https://grants.nih.gov/grants/funding/modular/modular.htm. When
submitting a modular budget, the applicant organization will include only the
PHS398 Modular Budget component. See Section 5.4 of the SF424 (R&R) Application Guide for further
instructions regarding the use of the PHS398 Modular Budget component.

Foreign organizations may not submit modular budgets.
See NOT-OD-06-096.

Special Instructions
for Applications Requesting $500,000 (direct costs) or More Per Year

Applicants requesting $500,000 or more in direct costs
for any year (excluding consortium F&A costs) must carry out the following
steps:

1) Contact the
IC program staff at least 6 weeks before submitting the application, i.e., as
you are developing plans for the study;

2) Obtain agreement from the IC staff that the IC will
accept your application for consideration for award; and,

3) Include the PHS398 Cover Letter component with the
application to identify the staff member and IC who agreed to accept assignment
of the application.

NIH has published new limitations on grant application
appendix materials to encourage applications to be as concise as possible while
containing the information needed for expert scientific review. See
https://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-018.html.

Do not use the Appendix to circumvent the page
limitations of the Research Plan component. An application that does not
observe the required page limitations may be delayed in the review process.

Note: While each section of the PHS398 Research Plan
component needs to be uploaded separately as a PDF attachment, applicants are
encouraged to construct the Research Plan component as a single document,
separating sections into distinct PDF attachments just before uploading the
files. This approach will enable applicants to monitor better formatting
requirements such as page limits. All attachments must be provided to NIH in
PDF format, filenames must be included with no spaces or special characters,
and a .pdf extension must be used.

Foreign Applications (Non-domestic (non-U.S.) Entity)

Indicate how the proposed project has specific
relevance to the mission and objectives of the IC and has the potential
for significantly advancing the health sciences in the United States.

Plan for Sharing
Research Data

Applicants requesting more
than $500,000 in direct costs in any year of the proposed research must include
a plan for sharing research data in their application. The funding organization
will be responsible for monitoring the data sharing policy (https://grants.nih.gov/grants/policy/data_sharing).

The precise content of the
data-sharing plan will vary, depending on the data being collected and how the
investigator is planning to share the data. Applicants who are planning to
share data may wish to describe briefly the expected schedule for data sharing,
the format of the final dataset, the documentation to be provided, whether or
not any analytic tools also will be provided, whether or not a data-sharing
agreement will be required and, if so, a brief description of such an agreement
(including the criteria for deciding who can receive the data and whether or
not any conditions will be placed on their use), and the mode of data sharing
(e.g., under their own auspices by mailing a disk or posting data on their
institutional or personal Web site, through a data archive or enclave).
Investigators choosing to share under their own auspices may wish to enter into
a data-sharing agreement. References to data sharing may also be appropriate in
other sections of the application.

The reasonableness of the
data sharing plan or the rationale for not sharing research data may be
assessed by the reviewers. However, reviewers will not factor the proposed data
sharing plan into the determination of scientific merit or the priority score.

Sharing Research
Resources

NIH policy expects that grant
recipients make unique research resources readily available for research
purposes to qualified individuals within the scientific community after
publication (See the NIH Grants Policy Statementhttps://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a sharing
research resources plan addressing how unique research resources will be shared
or explain why sharing is not possible.

The adequacy of the resources sharing plan and any
related data sharing plans will be considered by Program staff of the funding
organization when making recommendations about funding applications. The
effectiveness of the resource sharing will be evaluated as part of the
administrative review of each Non-Competing Grant
Progress Report (PHS 2590). See Section VI.3.,
“Reporting.”

Section V. Application Review Information

1. Criteria (Update: Enhanced review criteria have been issued for the evaluation of research applications received for potential FY2010 funding and thereafter - see NOT-OD-09-025).

Only the review criteria
described below will be considered in the review process.

2. Review and Selection Process

Applications
submitted for this funding opportunity will be assigned to the ICs on the basis
of established PHS referral guidelines.

Undergo a selection process in which only those
applications deemed to have the highest scientific merit, generally the
top half of applications under review, will be discussed and assigned a
priority score.

Receive a written critique.

Receive
a second level of review by the appropriate national advisory council or
board.

Applications submitted in
response to this funding opportunity will compete for available funds with all
other recommended applications. The following will be considered in making
funding decisions:

Scientific merit of the proposed project as
determined by peer review.

Availability of funds.

Relevance of program priorities.

The goals of NIH supported research are to advance our understanding of
biological systems, to improve the control of disease, and to enhance health.
In their written critiques, reviewers will be asked to comment on each of the
following criteria in order to judge the likelihood that the proposed research
will have a substantial impact on the pursuit of these goals. Each of these
criteria will be addressed and considered in assigning the overall score,
weighting them as appropriate for each application.

Significance

Approach

Innovation

Investigator

Environment

Note that an application does not need to be strong in all categories
to be judged likely to have major scientific impact and thus deserve a high
priority score. For example, an investigator may propose to carry out important
work that by its nature is not innovative but is essential to move a field
forward.

Significance: Does this study address an important problem? If the aims of the application
are achieved, how will scientific knowledge or clinical practice be advanced?
What will be the effect of these studies on the concepts, methods,
technologies, treatments, services, or preventative interventions that drive
this field?

Approach: Are the conceptual or clinical framework, design,
methods, and analyses adequately developed, well-integrated, well-reasoned, and
appropriate to the aims of the project? Does the applicant acknowledge
potential problem areas and consider alternative tactics? For applications designating
multiple PDs/PIs, is the leadership approach, including the designated roles
and responsibilities, governance, and organizational structure, consistent with
and justified by the aims of the project and the expertise of each of the
PDs/PIs??

Innovation: Is the project original and innovative? For example:
Does the project challenge existing paradigms or clinical practice; address an
innovative hypothesis or critical barrier to progress in the field? Does the
project develop or employ novel concepts, approaches or methodologies, tools,
or technologies for this area?

Investigators: Are the PD/PIs and other key personnel appropriately
trained and well suited to carry out this work? Is the work proposed
appropriate to the experience level(s) of the principal investigator(s) and
other researchers? Do the PD/PIs and investigative team bring complementary and
integrated expertise to the project (if applicable)?

Environment: Do(es) the scientific environment(s) in which the
work will be done contribute to the probability of success? Do the proposed
studies benefit from unique features of the scientific environment(s), or
subject populations, or employ useful collaborative arrangements? Is there
evidence of institutional support?

2.A. Additional Review Criteria

In addition to the above criteria, the following items
will continue to be considered in the determination of scientific merit and the
priority score:

Resubmission Applications (formerly “revised/amended”
applications): Are the responses to
comments from the previous scientific review group adequate? Are the
improvements in the resubmission application appropriate?

Protection of Human Subjects from Research Risk: The involvement of human
subjects and protections from research risk relating to their participation in
the proposed research will be assessed. See the “Human Subjects Sections” of
the PHS398 Research Plan component of the SF424 (R&R).

Inclusion of Women, Minorities and Children in Research: The adequacy of
plans to include subjects from both genders, all racial and ethnic groups (and
subgroups), and children as appropriate for the scientific goals of the
research will be assessed. Plans for the recruitment and retention of subjects
will also be evaluated. See the “Human Subjects Sections” of the PHS398
Research Plan component of the SF424 (R&R).

2.B. Additional Review Considerations

Budget and Period of Support: The reasonableness of the proposed budget and the
appropriateness of the requested period of support in relation to the proposed
research may be assessed by the reviewers. The priority score should not be
affected by the evaluation of the budget.

Applications from Foreign Organizations: Whether the project presents
special opportunities for furthering research programs through the use of
unusual talent, resources, populations, or environmental conditions in other
countries that are not readily available in the United States or that augment existing
U.S. resources will be assessed.

2.C. Sharing Research Data

Data Sharing Plan: The reasonableness of the
data sharing plan or the rationale for not sharing research data may be
assessed by the reviewers. However, reviewers will not factor the proposed data
sharing plan into the determination of scientific merit or the priority score.
The funding organization will be responsible for monitoring the data sharing
policy. https://grants.nih.gov/grants/policy/data_sharing.

2.D. Sharing Research
Resources

NIH policy expects that grant recipients make unique
research resources readily available for research purposes to qualified
individuals within the scientific community after publication (See the NIH
Grants Policy Statementhttps://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm#_Toc54600131).
Investigators responding to this funding opportunity should include a sharing
research resources plan addressing how unique research resources will be shared
or explain why sharing is not possible.

Program staff will be responsible for the
administrative review of the plan for sharing research resources.

The adequacy of the resources sharing plan and any
related data sharing plans will be considered by Program staff of the funding
organization when making recommendations about funding applications. The
effectiveness of the resource sharing will be evaluated as part of the
administrative review of each Non-Competing Grant
Progress Report (PHS 2590), See Section VI.3.,
“Reporting.”

3. Anticipated Announcement and Award Dates

Not applicable.

Section
VI. Award Administration Information

1. Award Notices

After the peer review of the application
is completed, the PD/PI will be able to access his or her Summary Statement
(written critique) via the NIH eRA Commons.

A formal notification
in the form of a Notice of Award (NoA) will be provided to the applicant
organization. The NoA signed by the grants management officer is the
authorizing document. Once all administrative and programmatic issues have been
resolved, the NoA will be generated via email notification from the awarding
component to the grantee business official.

Selection of an
application for award is not an authorization to begin performance. Any costs
incurred before receipt of the NoA are at the recipient's risk. These costs may
be reimbursed only to the extent considered allowable pre-award costs. See Section IV.5., “Funding Restrictions.”

We encourage your inquiries
concerning this funding opportunity and welcome the opportunity to answer
questions from potential applicants. Inquiries may fall into three areas:
scientific/research, peer review, and financial or grants management issues:

Human Subjects Protection:Federal regulations (45 CFR 46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety Monitoring Plan:Data and safety monitoring is required for all types
of clinical trials, including physiologic toxicity and dose-finding studies
(Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative
trials (Phase III). Monitoring should be commensurate with risk. The
establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide
for Grants and Contracts, https://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible (https://grants.nih.gov/grants/policy/data_sharing).

Investigators should seek guidance from their
institutions, on issues related to institutional policies and local IRB rules,
as well as local, State and Federal laws and regulations, including the Privacy
Rule. Reviewers will consider the data sharing plan but will not factor the
plan into the determination of the scientific merit or the priority score.

Access to Research Data through the Freedom of
Information Act:The Office of
Management and Budget (OMB) Circular A-110 has been revised to provide access
to research data through the Freedom of Information Act (FOIA) under some
circumstances. Data that are (1) first produced in a project that is supported
in whole or in part with Federal funds and (2) cited publicly and officially by
a Federal agency in support of an action that has the force and effect of law
(i.e., a regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of this amendment. NIH has provided
guidance at https://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm.
Applicants may wish to place data collected under this funding opportunity in a
public archive, which can provide protections for the data and manage the
distribution for an indefinite period of time. If so, the application should
include a description of the archiving plan in the study design and include information
about this in the budget justification section of the application. In addition,
applicants should think about how to structure informed consent statements and
other human subjects procedures given the potential for wider use of data
collected under this award.

Inclusion of
Women And Minorities in Clinical Research:It is the policy
of the NIH that women and members of minority groups and their sub-populations
must be included in all NIH-supported clinical research projects unless a clear
and compelling justification is provided indicating that inclusion is
inappropriate with respect to the health of the subjects or the purpose of the
research. This policy results from the NIH Revitalization Act of 1993 (Section
492B of Public Law 103-43). All investigators proposing clinical research
should read the "NIH Guidelines for Inclusion of Women and Minorities as
Subjects in Clinical Research” (https://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html);
a complete copy of the updated Guidelines is available at https://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm.
The amended policy incorporates: the use of an NIH definition of clinical
research; updated racial and ethnic categories in compliance with the new OMB
standards; clarification of language governing NIH-defined Phase III clinical
trials consistent with the SF424 (R&R) application; and updated roles and
responsibilities of NIH staff and the extramural community. The policy
continues to require for all NIH-defined Phase III clinical trials that: a) all
applications or proposals and/or protocols must provide a description of plans
to conduct analyses, as appropriate, to address differences by sex/gender
and/or racial/ethnic groups, including subgroups if applicable; and b)
investigators must report annual accrual and progress in conducting analyses,
as appropriate, by sex/gender and/or racial/ethnic group differences.

Inclusion of
Children as Participants in Clinical Research:The NIH
maintains a policy that children (i.e., individuals under the age of 21) must
be included in all clinical research, conducted or supported by the NIH, unless
there are scientific and ethical reasons not to include them.

Required
Education on the Protection of Human Subject Participants:NIH policy
requires education on the protection of human subject participants for all
investigators submitting NIH applications for research involving human subjects
and individuals designated as key personnel. The policy is available at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH Public Access Policy:NIH-funded
investigators are requested to submit to the NIH manuscript submission (NIHMS)
system (http://www.nihms.nih.gov/) at
PubMed Central (PMC) an electronic version of the author's final manuscript
upon acceptance for publication, resulting from research supported in whole or
in part with direct costs from NIH. The author's final manuscript is defined as
the final version accepted for journal publication, and includes all
modifications from the publishing peer review process.

NIH is
requesting that authors submit manuscripts resulting from 1) currently funded
NIH research projects or 2) previously supported NIH research projects if they
are accepted for publication on or after May 2, 2005. The NIH Public Access
Policy applies to all research grant and career development award mechanisms,
cooperative agreements, contracts, Institutional and Individual Ruth L.
Kirschstein National Research Service Awards, as well as NIH intramural
research studies. The Policy applies to peer-reviewed, original research
publications that have been supported in whole or in part with direct costs
from NIH, but it does not apply to book chapters, editorials, reviews, or
conference proceedings. Publications resulting from non-NIH-supported research
projects should not be submitted.

For more
information about the Policy or the submission process, please visit the NIH
Public Access Policy Web site at http://publicaccess.nih.gov// and view the Policy or other Resources and Tools, including the Authors' Manual.

Standards for
Privacy of Individually Identifiable Health Information:The Department
of Health and Human Services (HHS) issued final modification to the
"Standards for Privacy of Individually Identifiable Health Information",
the "Privacy Rule", on August 14, 2002. The Privacy Rule is a federal
regulation under the Health Insurance Portability and Accountability Act
(HIPAA) of 1996 that governs the protection of individually identifiable health
information, and is administered and enforced by the HHS Office for Civil
Rights (OCR).

Decisions about
applicability and implementation of the Privacy Rule reside with the researcher
and his/her institution. The OCR website (http://www.hhs.gov/ocr/)
provides information on the Privacy Rule, including a complete Regulation Text
and a set of decision tools on "Am I a covered entity?" Information
on the impact of the HIPAA Privacy Rule on NIH processes involving the review,
funding, and progress monitoring of grants, cooperative agreements, and
research contracts can be found at https://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH Grant
Applications or Appendices:
All applications and proposals for NIH funding must be
self-contained within specified page limitations. For publications listed in
the appendix and/or Progress report, Internet addresses (URLs) or PubMed
Central (PMC) submission identification numbers must be used for publicly
accessible on-line journal articles. Publicly accessible on-line journal
articles or PMC articles/manuscripts accepted for publication that are directly
relevant to the project may be included only as URLs or PMC
submission identification numbers accompanying the full reference in either
the Bibliography & References Cited section, the Progress Report
Publication List section, or the Biographical Sketch section of the NIH grant
application. A URL or PMC submission identification number citation may be
repeated in each of these sections as appropriate. There is no limit to the
number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:The Public
Health Service (PHS) is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2010," a PHS-led national
activity for setting priority areas. This FOA is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2010" at http://www.health.gov/healthypeople.

Authority and
Regulations:This
program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to
the intergovernmental review requirements of Executive Order 12372 or Health
Systems Agency review. Awards are made under the authorization of Sections 301
and 405 of the Public Health Service Act as amended
(42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR
Parts 74 and 92. All awards are subject to the terms and conditions, cost
principles, and other considerations described in the NIH
Grants Policy Statement.

The PHS strongly
encourages all grant recipients to provide a smoke-free workplace and
discourage the use of all tobacco products. In addition, Public Law 103-227,
the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in
some cases, any portion of a facility) in which regular or routine education,
library, day care, health care, or early childhood development services are
provided to children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

Loan
Repayment Programs:NIH encourages
applications for educational loan repayment from qualified health professionals
who have made a commitment to pursue a research career involving clinical,
pediatric, contraception, infertility, and health disparities related areas.
The LRP is an important component of NIH's efforts to recruit and retain the
next generation of researchers by providing the means for developing a research
career unfettered by the burden of student loan debt. Note that an NIH grant is
not required for eligibility and concurrent career award and LRP applications
are encouraged. The periods of career award and LRP award may overlap providing
the LRP recipient with the required commitment of time and effort, as LRP
awardees must commit at least 50% of their time (at least 20 hours per week
based on a 40 hour week) for two years to the research. For further
information, please see: http://www.lrp.nih.gov/.